Circadian rhythms adaptively respond and synchronize to light cues, and neuropeptides are emerging as important players in this light response pathway. One such neuropeptide, vasoactive intestinal peptide (VIP), appears to modulate light responses in the master circadian pacemaker of mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus. The purpose of the proposed studies is to gain a detailed understanding of how VIP-ergic signaling synchronizes the SCN to light. Experiments have been designed to answer the following questions: ls VIP critical for transmission of light-based information across anatomically localized and chemically-defined SCN subregions? Is it required for the gating of light responses in the SCN? Does lack of VIP affect electrical properties of individual SCN neurons? Does VIP regulate electrical responses to light-like phase shifts? Is this regulation anatomically heterogeneous? Are these effects temporally regulated? PUBLIC HEALTH RELEVANCE Using mice with genetic knockout of VIP, we will study gene expression and electrophysiology in the SCN to determine the specific role of VIP in light-based signaling. Not only will these experiments help clarify the role of this neuropeptide, it will also improve our understanding of how SCN neurons communicate with each other in the mammalian circadian system. In addition to the direct benefits for human health, knowledge from these findings may be extended to our understanding of how neuropeptides modulate sensory signals in other neural systems as well.